Association between DNA methylation of SORL1 5′-flanking region and mild cognitive impairment in type 2 diabetes mellitus

Objectives

In the present study, we examined whether DNA methylation of the sortilin-related receptor 1 (SORL1) 5′-flanking region is associated with the manifestation and clinical presentation of mild cognitive impairment in type 2 diabetes mellitus (T2DM).

Methods

Of 84 diabetic patients with mild cognitive impairment (MCI group), 78 diabetic patients without mild cognitive impairment (NMCI group) and 80 age-matched normal controls (NC group), the DNA methylation of the SORL1 5′-flanking region was completely analyzed. The SORL1 methylation ratios of the above three groups were compared statistically. Next, we investigated the correlation between the DNA methylation status and the clinical presentation of diabetes with or without cognitive impairment (MCI and NMCI groups).

Results

The methylation ratio (86.9%) of MCI patients was significantly higher than that in the NMCI patients (35.9%, P < 0.05) and in the NC group (11.3%, P < 0.05). Moreover, the diabetic patients with methylation alleles had greater ages, longer diabetes duration, lower MOCA scores and higher plasma amyloid Aβ 1-42 levels than those with unmethylation alleles (P < 0.05).

Conclusion

These results suggested that the DNA methylation of the SORL1 5′-flanking region may significantly influence the manifestation of mild cognitive impairment in T2DM, and might be associated with its neurocognitive presentation.